盐酸二甲双胍缓释片在中国健康受试者生物等效性研究  

Bioequivalence of metformin hydrochloride sustained-release tablets in Chinese healthy subjects

作　　者：赵彩芸[1] 吕媛[1] 魏敏吉[1] 崔洪[1] 张朴[1] 夏亚红[1] 田继红[1] 马雁[1] 刘燕[1] 王茜 吴景 王雅泰 ZHAO Cai-yun;LüYuan;WEI Min-ji;CUI Hong;ZHANG Pu;XIA Ya-hong;TIAN Ji-hong;MA Yan;LIU Yan;WANG Xi;WU Jing;WANG Ya-tai(Institute of Clinical Pharmacology,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院临床药理研究所,北京100034

出　　处：《中国临床药理学杂志》2020年第11期1562-1566,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价2种盐酸二甲双胍缓释片在中国健康受试者的生物等效性。方法按单中心、随机、开放、单剂量、两制剂、双周期、交叉设计。空腹和餐后条件下各入组32名健康受试者,随机交叉单次口服盐酸二甲双胍缓释片受试制剂与参比制剂0.5 g,用LC-MS/MS法测定血浆中二甲双胍的浓度,用WinNonlin 6.4软件按非房室模型计算药代动力学参数,并进行生物等效性评价。结果受试者口服盐酸二甲双胍缓释片受试制剂与参比制剂0.5 g后,空腹组血浆主要药代动力学参数如下:Cmax分别为(0.50±0.16)和(0.49±2.00)mg·L^-1,tmax分别为(4.66±1.00)和(5.11±1.11)h,AUC0-t分别为(3.93±1.28)和(3.92±1.65)mg·L^-1·h,AUC0-∞分别为(4.08±1.30)和(4.09±1.69)mg·L^-1·h;餐后组主要药代动力学参数如下:Cmax分别为(0.80±1.27)和(0.79±1.49)mg·L^-1,tmax分别为(7.22±1.20)和(7.20±1.01)h,AUC0-t分别为(7.27±1.52)和(6.97±1.58)mg·L^-1·h,AUC0-∞分别为(7.35±1.55)和(7.03±1.60)mg·L^-1·h。2种制剂的AUC0-t、AUC0-∞和Cmax经对数转换后90%置信区间空腹状态下分别为93.65%~111.46%,93.13%~111.21%和93.07%~114.12%;餐后状态下分别为100.83%~109.17%,100.92%~109.33%和97.72%~107.43%。结论无论是空腹还是餐后单次口服2种盐酸二甲双胍缓释片在中国健康受试者体内均具有生物等效性。Objective To evaluate the bioequivalence of the two metformin hydrochloride sustained-release tablets in Chinese healthy subjects.Methods This was a single-center,randomized,open,single dose,two-preparation,two period,crossover design.A total of 32 subjects in fasting state and 32 subjects in fed state were given single oral dose 0.5 g of test and reference metformin hydrochloride sustained-release tablets.The concentrations of metformin in plasma were determined by LC-MS/MS method.The pharmacokinetic parameters were calculated and the bioequivalence was compared by non-compartment model of WinNonlin 6.4 program.Results The main pharmacokinetics parameters of test and reference preparations of metformin were as follows:in fasting state,Cmax were(0.50±0.16)and(0.49±2.00)mg·L^-1,tmax were(4.66±1.00)and(5.11±1.11)h,AUC0-t were(3.93±1.28)and(3.92±1.65)mg·L^-1·h,AUC0-∞were(4.08±1.30)and(4.09±1.69)mg·L^-1·h;in fed state,Cmax were(0.80±1.27)and(0.79±1.49)mg·L^-1,tmax were(7.22±1.20)and(7.20±1.01)h,AUC0-t were(7.27±1.52)and(6.97±1.58)mg·L^-1·h,AUC0-∞were(7.35±1.55)and(7.03±1.60)mg·L^-1·h.The 90%CIs for AUC0-t,AUC0-∞and Cmax in fasting state were 93.65%-111.46%,93.13%-111.21%and 93.07%-114.12%;in fed state were 100.83%-109.17%,100.92%-109.33%and 97.72%-107.43%,respectively.Conclusion The exposures were equivalence between two metformin hydrochloride sustained-release tablets administered in fasting or fed state in Chinese healthy subjects.

关 键 词：盐酸二甲双胍缓释片 生物等效性 药代动力学 空腹和餐后 LC-MS/MS 

分 类 号：R977.15[医药卫生—药品]